Associations of birth weight and later life lifestyle factors with risk of cardiovascular disease in the USA: A prospective cohort study

Abstract

Background: Low birth weight has been associated with a greater risk of cardiovascular disease (CVD). However, the interaction between low birth weight and adult lifestyle factors on the risk of CVD remains unclear.

Methods: We included 20,169 men from the Health Professionals Follow-up Study (HPFS, 1986-2016), 52,380 women from the Nurses' Health Study (NHS, 1980-2018), and 85,350 women from the Nurses' Health Study II (NHS II, 1991-2017) in the USA who reported birth weight and updated data on adult body weight, smoking status, physical activity, and diet every 2-4 years. Incident cases of CVD, defined as a combined endpoint of fatal and nonfatal coronary heart disease (CHD) and stroke, were self-reported and confirmed by physicians through reviewing medical records.

Findings: During 4,370,051 person-years of follow-up, 16,244 incident CVD cases were documented, including 12,126 CHD and 4118 stroke cases. Cox proportional hazards regression models revealed an increased risk of CHD during adulthood across categories of decreasing birth weight in all cohorts (all P for linear trend <0.001). Additionally, we found an additive interaction between decreasing birth weight and unhealthy lifestyles on the risk of CHD among women, with a pooled relative excess risk due to interaction of 0.06 (95% CI: 0.04-0.08). The attributable proportions of the joint effect were 23.0% (95% CI: 11.0-36.0%) for decreasing birth weight alone, 67.0% (95% CI: 58.0-75.0%) for unhealthy lifestyle alone, and 11.0% (95% CI: 5.0-17.0%) for their additive interaction. Lower birth weight was associated with a greater stroke risk only among women, which was independent of later-life lifestyle factors.

Interpretation: Lower birth weight may interact synergistically with unhealthy lifestyle factors in adulthood to further increase the risk of CHD among women.

Funding: The National Institutes of Health grants.

Keywords: Birth weight; Cardiovascular disease; Lifestyle.

Figure 1

Flow diagram for cohort design, data collection, and exclusion criteria. Abbreviations: HPFS= the Health Professionals Follow-up Study (n = 20,169); NHS=the Nurses’ Health Study (n = 52,380); NHS II=the Nurses’ Health Study II (n = 85,350).

Figure 2

Crude cumulative incidence of cardiovascular disease according to birthweight category. A: the Health Professionals Follow-up Study (n = 20,169); B: the Nurses’ Health Study (n = 52,380); and C: the Nurses’ Health Study II (n = 85,350).

Figure 3

Hazard ratio (95% CI) of cardiovascular disease according to birth weight among men in the Health Professionals Follow-up Study (n = 20,169) and women in the Nurses’ Health Study (n = 52,380) and the Nurses’ Health Study II (n = 85,350). In the age-adjusted model, age in months (continuous) at the start of follow-up and the calendar year of the current questionnaire cycle were included as stratified variables to control for potential confounding by age, calendar time, and any possible interactions between these two timescales. Multivariable models were further adjusted for ethnicity (white, yes/no), family history of CVD (yes/no), as well as time-varying marital status (yes/no), living status (alone or not), menopausal status [premenopausal or postmenopausal (never, past, or current menopausal hormone use), women only], smoking status (never smoker, former smoker, current smoker: 1-14, 15-24, ≥25 cigarettes/d), alcohol drinking (0, 0.1-4.9, 5.0-14.9, 15.0-19.9, 20.0-29.9, ≥30 g/d), exercise (0, 0.01-1.0, 1.01-3.49, 3.5-5.99, ≥6 h/week), DASH diet score (5 categories), and body mass index (<21, 21-24.9, 25-29.9, 30-31.9, ≥32 kg/m²). P-values for the between-study test of heterogeneity were all above 0.05. P for nonlinearity was tested using restricted cubic splines. Abbreviations: NA=not applicable; HR= Hazard ratio; CI = confidence interval; HPFS= the Health Professionals Follow-up Study; NHS=the Nurses’ Health Study; NHS II=the Nurses’ Health Study II.